Glomerular filtration rate (GFR) is the sum of filtration rates in all functioning nephrons and so an estimation of the GFR provides a measure of functioning nephrons of the kidney. A decrease in GFR implies either progressive renal disease, or a reversible process causing decreased nephron function (eg, severe dehydration). One of the most common methods used for estimating GFR is creatinine clearance.

Creatinine is derived from the metabolism of creatine from skeletal muscle and dietary meat intake, and is released into the circulation at a relatively constant rate. Thus, the serum creatinine concentration is usually stable. Creatinine is freely filtered by glomeruli and not reabsorbed or metabolized by renal tubules. However, approximately 15% of excreted urine creatinine is derived from proximal tubular secretion. Because of the tubular secretion of creatinine, the creatinine clearance typically overestimates the true GFR by 10% to 15%.

Creatinine clearance is usually determined from measurement of creatinine in a 24-hour urine specimen and from a serum specimen obtained during the same collection period. The creatinine clearance is then calculated by the equation:

Decreased creatinine clearance indicates decreased glomerular filtration rate (GFR). This can be due to conditions such as progressive renal disease, or result from adverse effect on renal hemodynamics that are often reversible, including drug effects or decreases in effective renal perfusion (eg, volume depletion, heart failure).

Increased creatinine clearance is often referred to as hyperfiltration and is most commonly seen during pregnancy or in patients with diabetes mellitus, before diabetic nephropathy has occurred. It may also occur with large dietary protein intake.

A major limitation of creatinine clearance is that its accuracy worsens in relation to the amount of tubular creatinine secretion. Often as GFR declines, the contribution of urine creatinine from tubular secretion increases, further increasing the discrepancy between true GFR and measured creatinine clearance.